U.S. patent application number 12/421796 was filed with the patent office on 2010-06-10 for disposable diagnostic kit.
This patent application is currently assigned to Electronics and Telecommunications Research Institute. Invention is credited to Chul Huh, Bong Kyu Kim, Kyung Hyun Kim, Wanjoong Kim, Hyunsung Ko, Seon-Hee Park, Gun Yong Sung.
Application Number | 20100144020 12/421796 |
Document ID | / |
Family ID | 42231517 |
Filed Date | 2010-06-10 |
United States Patent
Application |
20100144020 |
Kind Code |
A1 |
Kim; Kyung Hyun ; et
al. |
June 10, 2010 |
DISPOSABLE DIAGNOSTIC KIT
Abstract
Provided is a disposable diagnostic kit capable of diagnosing
diseases. The disposable diagnostic kit includes a preprocessor, a
target material reactor, and a microfluidic channel. The
preprocessor filters target materials from a fluid containing
various biomaterials. The target material reactor includes a
diffraction grating on whose surface sensing materials reacting
with the target materials are immobilized. Herein, a wavelength of
light penetrated into the diffraction grating or a wavelength of
light reflected by the diffraction grating varies depending on the
target materials. The microfluidic channel moves the filtered fluid
from the preprocessor to the target material reactor.
Inventors: |
Kim; Kyung Hyun; (Daejeon,
KR) ; Kim; Wanjoong; (Goyang-si, KR) ; Kim;
Bong Kyu; (Daejeon, KR) ; Ko; Hyunsung;
(Seoul, KR) ; Huh; Chul; (Daejeon, KR) ;
Sung; Gun Yong; (Daejeon, KR) ; Park; Seon-Hee;
(Daejeon, KR) |
Correspondence
Address: |
AMPACC Law Group
3500 188th Street S.W., Suite 103
Lynnwood
WA
98037
US
|
Assignee: |
Electronics and Telecommunications
Research Institute
Daegeon
KR
|
Family ID: |
42231517 |
Appl. No.: |
12/421796 |
Filed: |
April 10, 2009 |
Current U.S.
Class: |
435/287.1 ;
422/400 |
Current CPC
Class: |
B01L 2400/0406 20130101;
B01L 2200/0684 20130101; B01L 2300/168 20130101; G01N 2021/0346
20130101; B01L 3/502707 20130101; B01L 3/502715 20130101; B01L
3/502746 20130101; B01L 2300/0851 20130101; B01L 2200/10 20130101;
B01L 2300/161 20130101; B01L 2300/0654 20130101; G01N 2021/7773
20130101; G01N 21/774 20130101; B01L 2200/025 20130101; B01L
2300/0816 20130101; B01L 2300/0681 20130101; G01N 21/03
20130101 |
Class at
Publication: |
435/287.1 ;
422/61 |
International
Class: |
C12M 1/34 20060101
C12M001/34; B01L 3/00 20060101 B01L003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 8, 2008 |
KR |
10-2008-123912 |
Claims
1. A disposable diagnostic kit comprising: a preprocessor filtering
target materials from a fluid containing various biomaterials; a
target material reactor comprising a diffraction grating on whose
surface sensing materials reacting with the target materials are
immobilized, wherein a wavelength of light penetrated into the
diffraction grating or a wavelength of light reflected by the
diffraction grating varies depending on the target materials; and a
microfluidic channel moving the filtered fluid from the
preprocessor to the target material reactor.
2. The disposable diagnostic kit of claim 1, further comprising a
fluid supply controller controlling the supply rate of the fluid
moving through the microfluidic channel.
3. The disposable diagnostic kit of claim 2, wherein the disposable
diagnostic kit is fabricated by coupling a top plate and a bottom
plate together in such a way that the facing planes of the top and
bottom plates are spaced apart from each other by a predetermined
distance.
4. The disposable diagnostic kit of claim 3, wherein the
microfluidic channel is formed by the facing planes of the top and
bottom plates.
5. The disposable diagnostic kit of claim 2, wherein the fluid
supply controller changes the sectional area of the microfluidic
channel to control the supply rate of the fluid.
6. The disposable diagnostic kit of claim 5, wherein the fluid
supply controller comprises a plurality of grooves formed at the
top or bottom plate to change the distance between the top and
bottom plates.
7. The disposable diagnostic kit of claim 3, wherein the top plate
comprises a fluid inlet configured to provide the fluid containing
the target materials directly to the preprocessor.
8. The disposable diagnostic kit of claim 3, wherein the top plate
comprises an air outlet configured to discharge air from the
microfluidic channel so that the fluid is moved by a capillary
force.
9. The disposable diagnostic kit of claim 3, wherein the bottom
plate has an alignment groove aligned with a reader that measures a
wavelength of light penetrated into the diffraction grating or a
wavelength of light reflected by the diffraction grating.
10. The disposable diagnostic kit of claim 3, wherein the top and
bottom plates have a coupling line formed along an edge thereof
where the top and bottom plates are coupled together.
11. The disposable diagnostic kit of claim 3, wherein the top and
bottom plates are formed of transparent materials penetrating or
reflecting light.
12. The disposable diagnostic kit of claim 1, wherein the
diffraction grating of the target material reactor comprises a
plurality of nanopatterns.
13. The disposable diagnostic kit of claim 12, wherein the
nanopatterns are periodically formed, and the light wavelength
varies depending on the period of the nanopatterns.
14. The disposable diagnostic kit of claim 1, wherein the sensing
materials are immobilized by a carboxyle group (--COOH), a thiol
group (--SH), a hydroxyl group (--OH), a silane group, an amine
group (--NH.sub.2), or an epoxy group induced on the surface of the
diffraction grating.
15. The disposable diagnostic kit of claim 14, wherein the reaction
between the sensing materials and the target materials includes
nucleic acid hybridization, antigen-antibody reaction, or enzyme
conjugation.
16. The disposable diagnostic kit of claim 1, wherein the fluid
containing the target materials includes a blood, and the
preprocessor passes plasma from the blood.
17. The disposable diagnostic kit of claim 1, wherein the
preprocessor, the microfluidic channel, the target material
reactor, and the fluid supply controller has a hydrophilic
surface.
18. The disposable diagnostic kit of claim 1, wherein the target
materials comprise at least one of nucleic acid, cell, virus,
protein, organic molecule, and inorganic molecule.
19. The disposable diagnostic kit of claim 18, wherein the nucleic
acid comprises at least one of DNA, RNA, PNA, LAN, and a mixture
thereof.
20. The disposable diagnostic kit of claim 18, wherein the protein
comprises at least one of enzyme, matrix, antigen, antibody ligand,
aptamer, and receptor.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This U.S. non-provisional patent application claims priority
under 35 U.S.C. .sctn.119 of Korean Patent Application No.
10-2008-0123912, filed on Dec. 8, 2008, the entire contents of
which are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention disclosed herein relates to a
disposable diagnostic kit, and more particularly, to a disposable
diagnostic kit capable of diagnosing diseases more simply.
[0003] A lap-on-a-chip is a device capable of analyze biomaterials,
in which the coupling and reaction between a sample and a reagent,
the creation of reactants, and the output of physical signals
corresponding to the reactants are performed in the single chip.
The lap-on-a-chip is used in hospitals or homes as a disposable
diagnostic kit that can rapidly diagnose diseases using a small
amount of biomaterial. Examples of the disposable diagnostic kit
are a home pregnancy diagnostic kit, a blood sugar diagnostic kit,
and an emergency-room AIDS diagnostic kit.
[0004] The disposable diagnostic kit requires a high-resolution
sensor in order to detect an extremely small amount of biomaterial,
qualitative information of biomaterial, and quantitative
information of biomaterial. Also, the disposable diagnostic kit
uses a technology for moving a body fluid such as blood or urine a
sensor, and a technology for changing the body fluid at the sensor
for detection by the naked eye. The disposable diagnostic kit may
also use a technology for electrochemically measuring a micro
current or voltage that is generated at an electrode according to a
biomaterial.
[0005] However, if various fluorescent materials, dyes, or
nanoparticles are used to identify biomaterials with the naked eye,
the biomaterial may be deformed by the coupling between the
color-developing material and the biomaterial.
[0006] Also, in the electrochemical method, an electrode must be
provided at the outside or inside of a disposable diagnostic kit in
order to measure a micro current or voltage. This may complicate
the fabrication process of the disposable diagnostic kit and may
increase the fabrication cost. Also, because the electrode is
provided at the disposable diagnostic kit, the electrical
characteristics may vary depending on the storage conditions (e.g.,
humidity and temperature) of the disposable diagnostic kit.
SUMMARY OF THE INVENTION
[0007] The present invention provides a disposable diagnostic kit
capable of diagnosing diseases more simply.
[0008] The object of the present invention is not limited to the
aforesaid, but other objects not described herein will be clearly
understood by those skilled in the art from descriptions below.
[0009] Embodiments of the present invention provide disposable
diagnostic kits including: a preprocessor filtering target
materials from a fluid containing various biomaterials; a target
material reactor comprising a diffraction grating on whose surface
sensing materials reacting with the target materials are
immobilized, wherein a wavelength of light penetrated into the
diffraction grating or a wavelength of light reflected by the
diffraction grating varies depending on the target materials; and a
microfluidic channel moving the filtered fluid from the
preprocessor to the target material reactor.
[0010] The details of other embodiments are included in the
detailed description and the drawings.
BRIEF DESCRIPTION OF THE FIGURES
[0011] The accompanying figures are included to provide a further
understanding of the present invention, and are incorporated in and
constitute a part of this specification. The drawings illustrate
exemplary embodiments of the present invention and, together with
the description, serve to explain principles of the present
invention. In the figures:
[0012] FIG. 1 is a perspective view of a disposable diagnostic kit
according to an exemplary embodiment of the present invention;
[0013] FIG. 2 is a view showing a top plate of the disposable
diagnostic kit according to an exemplary embodiment of the present
invention;
[0014] FIG. 3 is a view showing a bottom plate of the disposable
diagnostic kit according to an exemplary embodiment of the present
invention;
[0015] FIG. 4 is a cross-sectional view taken along a line I-I' of
FIG. 1; and
[0016] FIG. 5 is a view showing a target material reactor of the
disposable diagnostic kit according to an exemplary embodiment of
the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0017] Preferred embodiments of the present invention will be
described below in more detail with reference to the accompanying
drawings. The present invention may, however, be embodied in
different forms and should not be constructed as limited to the
embodiments set forth herein. Rather, these embodiments are
provided so that this disclosure will be thorough and complete, and
will fully convey the scope of the present invention to those
skilled in the art. Like reference numerals refer to like elements
throughout.
[0018] In the following description, the technical terms are used
only for explaining specific exemplary embodiments while not
limiting the present invention. The terms of a singular form may
include plural forms unless otherwise specified. The meaning of
"include," "comprise," "including," or "comprising," specifies a
property, a region, a fixed number, a step, a process, an element
and/or a component but does not exclude other properties, regions,
fixed numbers, steps, processes, elements and/or components.
[0019] Additionally, the embodiments in the detailed description
will be described with sectional views or plan views as ideal
exemplary views of the present invention. In the drawings, the
dimensions of layers and regions are exaggerated for clarity of
illustration. Areas exemplified in the drawings have general
properties, and are used to illustrate specific shapes of device
regions. Thus, these should not be construed as limiting to the
scope of the present invention.
[0020] In an exemplary embodiment, a blood is exemplified as a
fluid containing a target material, to which the present invention
is not limited. Other body fluids (e.g., urine and saliva)
containing a target material may be used to diagnose a target
material.
[0021] In the specification, a target material is a biomaterial
showing a specific nature, which is interpreted as having the same
meaning as target molecules, assays, or analytes. In an exemplary
embodiment, a biomaterial may be an antigen.
[0022] In the specification, a sensing material is a biomaterial
forming a specific binding to a target material, which is
interpreted as having the same meaning as probe molecules,
receptors, or acceptors. In an exemplary embodiment, a sensing
material may be an antibody.
[0023] Hereinafter, a disposable diagnostic kit according to an
exemplary embodiment of the present invention will be described in
detail with reference to the accompanying drawings.
[0024] FIG. 1 is a perspective view of a disposable diagnostic kit
according to an exemplary embodiment of the present invention. FIG.
2 is a view showing a top plate of the disposable diagnostic kit
according to an exemplary embodiment of the present invention. FIG.
3 is a view showing a bottom plate of the disposable diagnostic kit
according to an exemplary embodiment of the present invention. FIG.
4 is a cross-sectional view taken along a line I-I' of FIG. 1. FIG.
5 is a view showing a target material reactor of the disposable
diagnostic kit according to an exemplary embodiment of the present
invention.
[0025] Referring to FIGS. 1 to 5, a disposable diagnostic kit 100
according to an exemplary embodiment of the present invention
includes a top plate 110, a bottom plate 120, a preprocessor
130/135, a microfluidic channel 140, a target material reactor 150,
and a fluid supply controller 160.
[0026] Referring to FIG. 1, the disposable diagnostic kit 100 may
be fabricated by coupling the top plate 110 and the bottom plate
120 together. The top plate 110 and the bottom plate 120 may be
formed of a transparent material capable of transmitting light. For
example, the top plate 110 and the bottom plate 120 may be plastic
or glass substrates. Also, the top plate 110 and the bottom plate
120 may be transparent oxide substrates formed of a silicon nitride
(SiN), a titanium oxide (TiO.sub.2), a tantalum oxide
(Ta.sub.2O.sub.5), or an aluminum oxide (Al.sub.2O.sub.3). In other
words, the top plate 110 and the bottom plate 120 may be formed of
a material having a high index of refraction. Also, the top plate
110 and the bottom plate 120 may be formed of a transparent polymer
such as polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA),
polycarbonate (PC), cyclic olefin copolymer (COC), polyamide (PA),
polyethylene (PE), polypropylene (PP), polyphenylene ether (PPE),
polystyrene (PS), polyoxymethylene (POM), polyetheretherketone
(PEEK), polytetrafluoroethylene (PTFE), polyvinylchloride (PVC),
polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT),
fluorinated ethylenepropylene (FEP), or perfluoralkoxyalkane
(PFA).
[0027] Referring to FIGS. 1 to 4, the top plate 110 of the
disposable diagnostic kit 100 has a fluid inlet 112 formed to
inject a body fluid containing target materials. The fluid inlet
112 pierces the top plate 110, and transmits the body fluid
directly to the preprocessor 130/135. Accordingly, the fluid inlet
112 of the top plate 110 is formed corresponding to the
preprocessor 130/135 of the bottom plate 120.
[0028] A predetermined region of the top plate 110 may have at
least one air outlet 114 formed therein. The air outlet 114
discharges air from the microfluidic channel 140 so that the body
fluid injected through the fluid inlet 112 can flow smoothly
through the microfluidic channel 140. Also, the top plate 110 may
have a bonding member 116 bonded to the bottom plate 120. That is,
the air outlet 114 may be connected to the microfluidic channel 140
formed by the top and bottom plates 110 and 120.
[0029] Also, an edge of the top plate 110 may have a coupling line
118 formed to be coupled to the bottom plate 120. The coupling line
118 is formed so that the edges of the top and bottom plates 110
and 120 can be coupled together. The top and bottom plates 110 and
120 may be completely coupled by ultrasonic welding. For example,
the coupling line 118 serves as a welding line that is used for
ultrasonic welding of the top and bottom plates 110 and 120. The
welding line may be formed in the shape of a triangular pyramid and
groove.
[0030] The bottom plate 120 of the disposable diagnostic kit 100
has the preprocessor 130/135, the microfluidic channel 140, the
target material reactor 150, and the fluid supply controller 160
formed therein.
[0031] The preprocessor 130/135 selects only target materials
reacting or coupling with a sensing material, from a body fluid
containing various target materials. That is, the preprocessor
130/135 filters (or selects) a body fluid containing a target
material to be detected. For example, the preprocessor 130/135
removes hemocytes (i.e., unnecessary components) from a blood.
[0032] Examples of the body fluid include blood, urine, and saliva.
The body fluid may contain not only a target material to be
detected, but also nonspecific molecules not coupling with sensing
materials.
[0033] The body fluid may contain various target materials, and it
is necessary to remove unnecessary target materials from the body
fluid in order to accurately and rapidly detect a specific target
material to be diagnosed among the target materials.
[0034] For example, the body fluid contains various hemocytes and
plasmas, and contains protein components such as various cells,
lipid, catabolite, moisture, enzyme, antigen, and antibody. The
specific target material to be detected is mainly present in the
plasma. Examples of the target material include protein, nucleic
acid, virus, cell, organic molecule, and inorganic molecule. The
protein molecule may be any biomolecules such as antigen, antibody,
matrix protein, enzyme, and coenzyme. The nucleic acid may be DNA,
RNA, PNA, LNA, or a mixture thereof.
[0035] The preprocessor 130/135 includes a fluid storage chamber
130 and a micro filter 135. The fluid storage chamber 130 has a
bottom surface formed lower than the level of the bottom plate 120,
and stores a body fluid containing a target material. The micro
filter 135 is installed between the fluid storage chamber 130 and
the fluid inlet 112 of the top plate 110. The micro filter 135
filters off hemocytes from a body fluid, and passes only a plasma
containing a target material into the fluid storage chamber 135.
For example, the micro filter 135 may be a micro paper filter
having micro holes formed therein. The thickness of the micro paper
filter and the sizes of the micro holes may vary depending on the
sizes of target materials contained in a body fluid, or the amount
of a body fluid flowing into the preprocessor 130/135.
[0036] The blood filtered by the preprocessor 130/135 may move
through the microfluidic channel 140 to the target material reactor
150. The microfluidic channel 140 moves the blood filtered by the
preprocessor 130/135 to the target material reactor 150. The
microfluidic channel 140 is formed by coupling the bottom of the
top plate 110 with the top of the bottom plate 120 in such a way
that they are spaced apart from each other by a predetermined
distance. Herein, the distance between the top and bottom plates
110 and 120 is controlled to generate a sufficient capillary force.
By the capillary force, the preprocessed blood can pass the
microfluidic channel 140. For example, the microfluidic channel 140
may have a diameter or height `h` of about 1 nm to about 40 .mu.m.
Also, the microfluidic channel 140 may be hydrophilically
surface-treated so that the preprocessed blood can move
smoothly.
[0037] The target material reactor 150 biochemically reacts or
couples sensing materials with target materials to be detected.
Without labeling material, light is irradiated onto the target
material reactor 150 to detect if there is a biochemical reaction
or coupling between a sensing material and a specific target
material. The target material reactor 150 may be a resonance
reflection filter that measures a wavelength change of light by the
biochemical reaction or coupling between target materials and
sensing materials to detect a specific target material. The
resonance reflection filter uses the peak of a reflection spectrum
created by diffraction gratings that can serve as a high-refractive
waveguide. The reflection spectrum, which is created by a coupling
with a mode where the light diffracted by the diffraction gratings
is guided through the high-refractive waveguide, is narrow in
linewidth, thus making it possible to implement a high-resolution
biosensor.
[0038] Referring to FIG. 5, the target material reactor 150
includes nanopatterns 152 that generate resonant reflected light.
Light penetrated into the nanopatterns 152 or reflected by the
nanopatterns 152. And, a wavelength of light penetrated into the
nanopatterns 152 or a wavelength of light reflected by the
nanopatterns 152 varies depending on the reaction between the
sensing materials and the target materials. The number of the
nanopatterns 152 may be determined according to the amount or
number of sensing materials for a disease or a symptom to be
diagnosed. The nanopatterns 152 may be formed through a
photolithography process, an electron-beam lithography process, or
an imprint process that transfers nanopatterns using a stamp. Also,
the disposable diagnostic kit 100 including the nanopatterns 152
may be formed through an injection molding process. The injection
molding was carried out by using a metal mold having nano patterns
for target material reactor 150. Therefore, it is possible to mass
produce the disposable diagnostic kit 100. For example, the
nanopatterns 152 may be a periodically-repeated line-and-space
pattern that generates resonant reflected light such as the 780nm
band. The nanopatterns 152 may be formed in a square region, and
the period `p` and arrangement of the nanopatterns 152 may vary
depending on the wavelength of desirable resonant reflected
light.
[0039] Sensing materials, which react or couple with specific
target materials of a disease or a symptom to be diagnosed, are
immobilized on the surfaces of the nanopatterns 152 of the target
material reactor 150. The sensing materials may be protein, cell,
virus, nucleic acid, organic molecule, and inorganic molecule,
according to the target material to be detected. The protein may be
any target materials such as antigen, antibody, matrix protein,
enzyme, and coenzyme. The nucleic acid may be DNA, RNA, PNA, LNA,
or a mixture thereof.
[0040] The sensing materials may be immobilized on the surfaces of
the nanopatterns 152 by chemical adsorption, covalent-binding,
electrostatic attraction, co-polymerization, or avidin-biotin
affinity system.
[0041] That is, the sensing materials may be immobilized on the
surfaces of the nanopatterns 152 directly or indirectly by using
organic molecules as intermediate medium molecules. Also, a
functional group may be induced on the surfaces of the nanopatterns
152 in order to immobilize the target materials on the nanopatterns
152. For example, functional groups, such as a carboxyle group
(--COOH), a thiol group (--SH), a hydroxyl group (--OH), a silane
group, an amine group, and an epoxy group, may be induced on the
surfaces of gold nanoparticles.
[0042] Also, a space between the nanopatterns 152 may be blocked so
that the sensing materials are not immobilized therein.
[0043] Also, the fluid supply controller 160 may be formed on the
bottom plate 120 of the disposable diagnostic kit 100 to control
the supply rate of the blood supplied to the target material
reactor 150.
[0044] That is, the fluid supply controller 160 serves as a time
gate that delays the flow of a preprocessed blood. Accordingly, the
fluid supply controller 160 enables a sensing material and a
specific target material to react with each other for a sufficient
time.
[0045] The fluid supply controller 160 may be formed by modifying
the shape of the microfluidic channel 140 through which a blood
flows. That is, the fluid supply controller 160 may control the
fluid supply by changing the sectional area of the microfluidic
channel 140. For example, the fluid supply controller 160 may
include microgrooves formed at the bottom plate 120. The size of
number of the microgrooves may vary depending on the reaction times
according to the sensing material and the specific target
materials. Also, the microgrooves may be surface-treated with
hydrophobic materials.
[0046] The fluid supply controller 160 including the microgrooves
locally increases the diameter of the microfluidic channel 140,
thereby making it possible to reduce the capillary force of the
microfluidic channel 140. Accordingly, the flow rate of the blood
flowing through the microfluidic channel 140 can be reduced.
[0047] That is, the disposable diagnostic kit 100 includes a region
where the distance between the top and bottom plates 110 and 120 is
equal to `h` (i.e., a region of the microfluidic channel 140), and
a region where the distance between the top and bottom plates 110
and 120 is greater than `h` (i.e., a region of the fluid supply
controller 160).
[0048] Also, as illustrated in FIG. 4, at least one alignment
groove 122 may be formed in a predetermined region of the bottom
plate 120, which is to be aligned with or mounted on a reader (not
shown) for detecting a resonant reflected light generated by the
target material reactor 160 when a specific target material is
detected. In another embodiment, at least one alignment groove 122
may be formed at the top plate 110.
[0049] The reader may detect a target material by measuring the
wavelength of a resonant reflected light before/after the coupling
or reaction of the target material with sensing materials.
[0050] As described above, the present invention uses plastic
materials to form the top and bottom plates, thus making it
possible to provide an inexpensive disposable diagnostic kit.
[0051] The disposable diagnostic kit of the present invention
includes the preprocessor, thus making it possible to directly
inject a biomaterial detecting sample (i.e., a blood) into the
diagnostic kit without preprocessing. Therefore, the present
invention can detect/analyze a biomaterial rapidly. Also, the
present invention can detect a biomaterial in a label-free fashion
without limitation on the environmental conditions for detection of
the biomaterial.
[0052] That is, the present invention performs fluid movement and
biomaterial detection in the single diagnostic kit, thus making it
possible to diagnose a disease more simply.
[0053] The above-disclosed subject matter is to be considered
illustrative, and not restrictive, and the appended claims are
intended to cover all such modifications, enhancements, and other
embodiments, which fall within the true spirit and scope of the
present invention. Thus, to the maximum extent allowed by law, the
scope of the present invention is to be determined by the broadest
permissible interpretation of the following claims and their
equivalents, and shall not be restricted or limited by the
foregoing detailed description.
* * * * *